The DOI matches its Crossref record; 10 of the 10 references it cites were found in a registry or an index.
Structural mechanism of cytosolic DNA sensing by cGAS
Open accessAbstract
Cytosolic DNA arising from intracellular bacterial or viral infections is a powerful pathogen-associated molecular pattern (PAMP) that leads to innate immune host defence by the production of type I interferon and inflammatory cytokines. Recognition of cytosolic DNA by the recently discovered cyclic-GMP-AMP (cGAMP) synthase (cGAS) induces the production of cGAMP to activate the stimulator of interferon genes (STING). Here we report the crystal structure of cGAS alone and in complex with DNA, ATP and GTP along with functional studies. Our results explain the broad DNA sensing specificity of cGAS, show how cGAS catalyses dinucleotide formation and indicate activation by a DNA-induced structural switch. cGAS possesses a remarkable structural similarity to the antiviral cytosolic double-stranded RNA sensor 2′-5′oligoadenylate synthase (OAS1), but contains a unique zinc thumb that recognizes B-form double-stranded DNA. Our results mechanistically unify dsRNA and dsDNA innate immune sensing by OAS1 and cGAS nucleotidyl transferases.
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Cites
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Cyclic GMP-AMP Synthase Is a Cytosolic DNA Sensor That Activates the Type I Interferon Pathway
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STING is an endoplasmic reticulum adaptor that facilitates innate immune signalling
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STING regulates intracellular DNA-mediated, type I interferon-dependent innate immunity
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AIM2 recognizes cytosolic dsDNA and forms a caspase-1-activating inflammasome with ASC
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Self-citationAIM2 activates the inflammasome and cell death in response to cytoplasmic DNA
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CGAS produces a 2′-5′-linked cyclic dinucleotide second messenger that activates STING.
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Self-citationSTING is a direct innate immune sensor of cyclic di-GMP
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Cited by
Regulation and function of the cGAS–STING pathway of cytosolic DNA sensing
Chen, Q., Sun, L., & Chen, Z. J. (2016) · Nature Immunology · doi:10.1038/ni.3558 · Cited by 2,333
The cGAS–STING pathway as a therapeutic target in inflammatory diseases
Decout, A., Katz, J. D., Venkatraman, S., & Ablasser, A. (2021) · Nature Reviews Immunology · doi:10.1038/s41577-021-00524-z · Cited by 2,309
Self-citationMolecular mechanisms and cellular functions of cGAS–STING signalling
Hopfner, K.-P., & Hornung, V. (2020) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-020-0244-x · Cited by 2,052
Self-citationDNA sensing by the cGAS–STING pathway in health and disease
Motwani, M., Pesiridis, S., & Fitzgerald, K. A. (2019) · Nature Reviews Genetics · doi:10.1038/s41576-019-0151-1 · Cited by 1,467
The Cytosolic DNA-Sensing cGAS–STING Pathway in Cancer
Kwon, J., & Bakhoum, S. F. (2020) · Cancer Discovery · doi:10.1158/2159-8290.cd-19-0761 · Cited by 1,293
Metadata
- Authors
- Civril, F., Deimling, T., de Oliveira Mann, C. C., Ablasser, A., Moldt, M., Witte, G., Hornung, V., & Hopfner, K.-P.
- Venue
- Nature
- Published
- 2013-05-30
- Volume
- 498
- Issue
- 7454
- Pages
- 332-337
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2119864130
- Cited by
- 884
- References
- 10
- FWCI
- 22.34
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Civril, F., Deimling, T., de Oliveira Mann, C. C., Ablasser, A., Moldt, M., Witte, G., Hornung, V., & Hopfner, K.-P. (2013). Structural mechanism of cytosolic DNA sensing by cGAS. Nature. https://doi.org/10.1038/nature12305
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